What is the recommended management of ICU delirium in a patient with chronic liver disease and chronic kidney disease?

Management of ICU Delirium in Patients with Chronic Liver Disease and Chronic Kidney Disease

First-Line Approach: Non-Pharmacological Interventions

Maximize non-pharmacological multicomponent interventions before considering any medication, as these are the only interventions proven to reduce delirium incidence, duration, ICU length of stay, and mortality. 1

Immediate Implementation Steps

• Early mobilization is the single most effective intervention—get the patient out of bed and walking as soon as hemodynamically stable, regardless of CLD or CKD status, as this reduces both delirium incidence and duration while increasing ventilator-free days. 2, 1

• Optimize sleep-wake cycles by controlling light exposure (bright during day, dark at night), clustering care activities to avoid nighttime interruptions, and minimizing alarm noise. 1

• Provide cognitive stimulation and reorientation using clocks, calendars, familiar objects from home, and frequent verbal reorientation by staff and family members. 1

• Ensure sensory optimization by making certain the patient has glasses and hearing aids in place, as sensory deprivation worsens delirium. 1

• Systematically screen for delirium using validated tools like CAM-ICU or ICDSC at least twice daily to enable early detection. 1

Address Reversible Causes Specific to CLD/CKD

• In CLD patients, evaluate for hepatic encephalopathy (ammonia level, lactulose adequacy), spontaneous bacterial peritonitis, gastrointestinal bleeding, and electrolyte disturbances (particularly hyponatremia). 2

• In CKD patients, assess for uremia, electrolyte imbalances (hyperkalemia, hypocalcemia, hyperphosphatemia), metabolic acidosis, and volume overload causing hypoxia. 2

• Review all medications for anticholinergic burden, dose adjustments needed for renal clearance, and hepatic metabolism—many sedatives and analgesics accumulate in organ dysfunction. 3

• Correct metabolic disturbances including hypoxia, urinary retention, constipation, and pain, as these are modifiable triggers. 3

Sedation Strategy in Mechanically Ventilated Patients

Use dexmedetomidine rather than benzodiazepines for sedation in mechanically ventilated patients with delirium (except in alcohol or benzodiazepine withdrawal), as this reduces delirium duration by approximately 20%. 2, 1

• Implement analgesia-first sedation by treating pain adequately before adding sedatives, as untreated pain worsens delirium. 2, 1

• Maintain light levels of sedation through daily sedation interruption or continuous titration to the lightest effective dose. 2, 1

• Avoid benzodiazepines whenever possible, as they are an independent risk factor for developing delirium in ICU patients. 2, 1

Pharmacological Management: When and What to Use

Critical Evidence on Antipsychotics

Antipsychotics should NOT be used routinely for ICU delirium, as six randomized controlled trials demonstrate they do not reduce delirium duration, mechanical ventilation time, ICU length of stay, or mortality. 1, 4

Narrow Indications for Antipsychotic Use

Antipsychotics are justified only for: 1, 3

• Severe distress from hallucinations or delusions with fearfulness
• Agitation posing physical harm to the patient or staff
• Agitation preventing delivery of essential medical care

Antipsychotic Selection in CLD/CKD Patients

If antipsychotic use is unavoidable, quetiapine is preferred in patients with organ dysfunction due to lower risk of QTc prolongation and extrapyramidal symptoms. 1

• Quetiapine dosing: Start 12.5–25 mg every 12 hours via oral or gastric tube, titrate to 25–50 mg twice daily as needed, maximum 100–200 mg daily with extreme caution. 1

• Haloperidol should be avoided entirely despite historical use, as there is no adequately powered evidence for efficacy and it significantly prolongs QTc interval. 1, 4, 3

• Olanzapine 2.5–5 mg may be used as second-line with moderate QTc risk but safer than haloperidol. 1

Absolute Contraindications

• Do not use antipsychotics in patients with baseline QTc >500 ms, history of torsades de pointes, or concurrent QT-prolonging medications (common in ICU patients). 2, 1

• Never use rivastigmine or other cholinesterase inhibitors, as they increase mortality and prolong delirium duration. 2, 1

• Avoid haloperidol in Parkinson's disease due to severe risk of extrapyramidal symptoms and neuroleptic malignant-like syndrome. 4

Monitoring Protocol for Antipsychotic Therapy

• Obtain baseline ECG before initiating any antipsychotic and repeat 2–4 hours after first dose. 1

• Perform daily ECGs while on therapy; discontinue if QTc lengthens ≥60 ms from baseline or exceeds 550 ms. 1

• Correct electrolytes (potassium, magnesium, calcium) before and during treatment, as these abnormalities are common in CLD/CKD and worsen arrhythmia risk. 1

• Monitor for extrapyramidal symptoms (dystonia, akathisia, parkinsonism) throughout therapy. 1

• Discontinue antipsychotics immediately once acute distressing symptoms resolve to avoid unnecessary morbidity. 3

Special Considerations for CLD/CKD Populations

Chronic Liver Disease Considerations

• Hepatic encephalopathy may mimic or coexist with delirium—ensure adequate lactulose therapy and rifaximin if indicated before attributing confusion solely to ICU delirium. 2

• Antipsychotic metabolism is impaired in cirrhosis, requiring lower starting doses and slower titration. 1

• Avoid medications with high hepatic first-pass metabolism when possible, as drug accumulation increases toxicity risk. 2

Chronic Kidney Disease Considerations

• Uremia itself causes encephalopathy—consider whether dialysis adequacy is optimized before adding psychotropic medications. 2

• Dose-adjust all renally cleared medications, including active metabolites of antipsychotics that accumulate in renal failure. 2

• Discuss goals of care with family if patient has severely limited life expectancy, low quality of life, or progressive deterioration, as conservative management may be more appropriate than aggressive delirium treatment. 2

Critical Pitfalls to Avoid

• Do not reflexively prescribe haloperidol despite its historical popularity—it lacks efficacy data and carries significant cardiac risk. 1, 4

• Do not use antipsychotics prophylactically to prevent delirium, as no evidence supports this practice and it exposes patients to unnecessary harm. 2, 1, 3

• Do not overlook hypoactive delirium, which is the most common presentation (especially in palliative settings) and often does not require antipsychotic therapy. 2, 1

• Do not add benzodiazepines as first-line unless delirium is due to alcohol or benzodiazepine withdrawal, as they worsen outcomes. 2, 1, 3

• Do not continue antipsychotics beyond resolution of acute symptoms, as prolonged use increases morbidity and cost without benefit. 3

When to Escalate Care

Consult palliative care or psychiatry when: 1

• Delirium remains refractory despite optimized non-pharmacologic and pharmacologic measures
• Consideration of palliative sedation for terminal delirium arises
• Uncertainty exists regarding risk-benefit balance of antipsychotic use with marked organ dysfunction